Methods are known for performing a plurality of sequential tests or reactions at loci on a matrix by attachment of molecules to a solid phase. Typically, a solid phase is prepared having a free functional group such as a hydroxy group, amino group, etc. and linking groups are attached to the surface by way of covalent linkages. These linkers serve as "handles" to which molecules may be attached for sequential synthesis of such linear molecules as polypeptides and polynucleotides. A disadvantage of such solid state synthesis is that the entire substrate or a large portion of the substrate must be exposed to a single reagent, such as the reagent which is the next molecule to be attached to the substrate, a rinsing agent or a deprotecting agent.
In some instances, locations on the substrate can be selectively treated if the reaction to be conducted is photolytic in nature, so masks may be prepared to expose selected areas to the activating radiation. However, an obvious disadvantage is that reactions must be devise which can be conducted by photolytic activation and different masks must be used to shield portions of the substrate at which the reaction is undesired.
The present invention provides a method whereby reactions may be conducted on noncontiguous microdrop-sized loci on a substrate. Since the reagents according to the present invention are in liquid form, virtually any chemical reaction which may be conducted in solution or suspension may be performed.
It is therefore an object of the present invention to provide a method and apparatus for performing a plurality of sequential reactions on a substrate whereby the reactions are conducted on microdrop-sized loci and, if desired, a different sequence of reactions may be conducted at each locus.
Furthermore, an object of the present invention is to provide a method and apparatus for conducting a plurality of sequential reactions on a matrix using liquid reagents whereby the chemical reactions may be performed in solution or suspension.
These and other objects of the invention will be apparent from the following description, the appended claims and from the practice of the invention as described herein.